Midkine-Notch2 Pathway Mediates Excessive Proliferation of Airway Smooth Muscle Cells in Chronic Obstructive Lung Disease.

Inflammation-induced proliferation of airway smooth muscle cells (ASMCs) and subsequent airway remodeling is a hallmark of chronic obstructive lung disease (COPD). The role of midkine (MK) in COPD is unclear. In this work, we explored the role of MK-Notch2 signaling in COPD by inhibiting the expression of MK using lentivirus shRNA in ASMCs in vitro and instillation of AAV9-MK in the airway of a COPD rat model in vivo. The results demonstrated that LPS decreased ASMC migration and proliferation, increased apoptosis and induced the expression of MK and Notch2 signaling molecules. Inhibition of MK exacerbated the changes in migration and proliferation but decreased the expression of MK and Notch2 signaling molecules. Rats treated with smoke fumigation and LPS showed features of COPD. The small airways of COPD rats were remodeled and lung function was significantly reduced. The expressions of TGF-ß, ICAM-1, HA, MMP-9, PC-III, and LN in BALF and the expression of MK and Notch2 signaling molecules were significantly increased in the COPD rats compared with controls. Inhibition of MK reversed these changes. In conclusion, the MK-Notch2 pathway plays a key role in airway remodeling induced by ASMC proliferation. Targeting the MK-Notch2 pathway may be a new strategy for improving airway remodeling and preventing progressive decline of pulmonary function in COPD.

Multiple indicators of rice remains and the process of rice domestication: A case study in the lower Yangtze River region, China.

The process of rice domestication has been studied for decades based on changing morphological characteristics in assemblages of both macroremains, such as charred seeds and spikelet bases, and microremains, such as phytoliths, esp. bulliform and double-peaked phytoliths. The applicability of these indicators in determining if a specific assemblage is wild or domesticated, however, is rarely discussed. To understand the significance of these indicators in the determination of domestication, we collected 38 archaeological samples from eight Neolithic sites, dating from 10-2ka BP, in the lower Yangtze River region to analyze and compare the changes of these different indicators over eight thousand years. The data demonstrate that the comprehensive analysis of multiple indicators may be the best method to study the process of rice domestication developed thus far. An assemblage of rice remains can be identified as domesticated forms if they meet the following criteria simultaneously: 1) the proportion of domesticated-type bulliform phytoliths is more than 73%; and 2) the proportion of domesticated-type rice spikelet bases is higher than 75%. Furthermore, we found that each indicator tends to change steadily and gradually over time, and each stabilized at a different time, suggesting that the characteristics of domesticated rice developed slowly and successively. Changes of multiple indicators during the period between 10,000-2,000 yr BP indicate that the process of rice domestication in the lower Yangtze River region lasted as long as ca. 6,000 years during the Neolithic, and can be divided into three stages with the turning points in the middle Hemudu-late Majiabang culture (6,500-5,800yr BP) and the late Liangzhu culture (4,600-4,300yr BP).

Correction: Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

[This corrects the article DOI: 10.1371/journal.pone.0187405.].

Publisher Correction: The early history of wheat in China from 14C dating and Bayesian chronological modelling.

In the version of this Article originally published, the x and y axis labels in Fig. 1 were switched over; the correct labels are: 'Longitude (° N)' on the x axis, and 'Latitude (° E)' on the y axis. This figure has now been amended in all versions of the Article.

The early history of wheat in China from 14C dating and Bayesian chronological modelling.

Wheat is regarded as one of the most important West Asian domesticates that were introduced into Late Neolithic/Early Bronze Age China. Despite a growing body of archaeological data, the timing and routes of its dispersal remain controversial. New radiocarbon (14C) dating evidence from six archaeological sites in the Shandong and Liaoning Peninsulas and Bayesian modelling of available 14C data from China suggest that wheat appeared in the lower Yellow River around 2600 Before Common Era (BCE), followed by Gansu and Xinjiang around 1900 BCE and finally occurred in the middle Yellow River and Tibet regions by 1600 BCE. These results neither support long-standing hypotheses of a progressive spread of wheat agriculture from Xinjiang or Gansu to eastern China nor suggest a nearly synchronous appearance in this vast zone, but corroborate transmission to lower Yellow River elites as an exotic good through cultural interactions with the Eurasian steppe along north-south routes.

Changes in cardiac arrest patients' temperature management after the publication of 2015 AHA guidelines for resuscitation in China.

A survey was performed to assess the current management of targeted temperature management (TTM) in patients following cardiac arrest (CA) and whether healthcare providers will change target temperature after publication of 2015 American Heart Association guidelines for resuscitation in China. 52 hospitals were selected from whole of China between August to November 2016. All healthcare providers in EMs and/or ICUs of selected hospitals participated in the study. 1952 respondents fulfilled the survey (86.8%). TTM in CA patients was declared by 14.5% of physicians and 6.7% of the nurses. Only 4 of 64 departments, 7.8% of physicians and 5.7% of the nurses had implemented TH for CA patients. Since the publication of 2015 AHA guidelines, 33.6% of respondents declared no modification of target temperature, whereas 51.5% declared a target temperature's change in future practice. Respondents were more likely to choose 35∼36 °C-TTM (54.7%) after guidelines publication, as compared to that before guidelines publication they preferred 32∼34 °C-TTM (54.0%). TTM for CA patients was still in the early stage in China. Publication of 2015 resuscitation guidelines did have impact on choice of target temperature among healthcare providers. They preferred 35∼36 °C-TTM after guidelines publication.

Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

Today, farmers in many regions of eastern Asia sow their barley grains in the spring and harvest them in the autumn of the same year (spring barley). However, when it was first domesticated in southwest Asia, barley was grown between the autumn and subsequent spring (winter barley), to complete their life cycles before the summer drought. The question of when the eastern barley shifted from the original winter habit to flexible growing schedules is of significance in terms of understanding its spread. This article investigates when barley cultivation dispersed from southwest Asia to regions of eastern Asia and how the eastern spring barley evolved in this context. We report 70 new radiocarbon measurements obtained directly from barley grains recovered from archaeological sites in eastern Eurasia. Our results indicate that the eastern dispersals of wheat and barley were distinct in both space and time. We infer that barley had been cultivated in a range of markedly contrasting environments by the second millennium BC. In this context, we consider the distribution of known haplotypes of a flowering-time gene in barley, Ppd-H1, and infer that the distributions of those haplotypes may reflect the early dispersal of barley. These patterns of dispersal resonate with the second and first millennia BC textual records documenting sowing and harvesting times for barley in central/eastern China.

Heparanase Mediates Intestinal Inflammation and Injury in a Mouse Model of Sepsis.

Heparanase, a heparan sulfate (HS)-specific endoglycosidase, plays an important role in inflammation and mediates acute pulmonary and renal injuries during sepsis. To explore its role in septic intestinal injury, a non-anticoagulant heparanase inhibitor, N-desulfated/re- N-acetylated heparin (NAH), was administrated to a mouse sepsis model induced by cecal ligation and puncture (CLP). Immunohistochemical staining revealed massive shedding of HS from the intestinal mucosal surfaces after CLP, and effective inhibition of heparanase by NAH was confirmed by markedly reduced HS shedding. Following CLP, intestinal expression of heparanase was increased, whereas pretreatment with NAH reduced the sepsis-induced upregulation of heparanase expression. Meanwhile, CLP led to shedding of syndecan-1 and upregulated expression of proteases such as matrix metalloprotease-9 and urokinase-type plasminogen activator in the intestine, whereas NAH markedly suppressed syndecan-1 shedding and protease upregulation following CLP. In addition, pretreatment with NAH attenuated intestinal injury, inhibited neutrophil infiltration and suppressed the production of inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) in the intestine during sepsis, and it also significantly reduced the elevation of inflammatory cytokines in the serum 24 hr after CLP. Our findings demonstrate that the activation of intestinal heparanase contributes to intestinal injury during early sepsis by facilitating the destruction of mucosal epithelial glycocalyx and promoting inflammatory responses.

Archaeointensity results spanning the past 6 kiloyears from eastern China and implications for extreme behaviors of the geomagnetic field.

Variations of the Earth's geomagnetic field during the Holocene are important for understanding centennial to millennial-scale processes of the Earth's deep interior and have enormous potential implications for chronological correlations (e.g., comparisons between different sedimentary recording sequences, archaeomagnetic dating). Here, we present 21 robust archaeointensity data points from eastern China spanning the past ∼6 kyr. These results add significantly to the published data both regionally and globally. Taking together, we establish an archaeointensity reference curve for Eastern Asia, which can be used for archaeomagnetic dating in this region. Virtual axial dipole moments (VADMs) of the data range from a Holocene-wide low of ∼27 to "spike" values of ∼166 ZAm2 (Z: 1021). The results, in conjunction with our recently published data, confirm the existence of a decrease in paleointensity (DIP) in China around ∼2200 BCE. These low intensities are the lowest ever found for the Holocene and have not been reported outside of China. We also report a spike intensity of 165.8 ± 6.0 ZAm2 at ∼1300 BCE (±300 y), which is either a prelude to or the same event (within age uncertainties) as spikes first reported in the Levant.

Effect of partial splenic embolization on the immune function of cirrhosis patients with hypersplenism.

OBJECTIVE: To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism. METHODS: Patients involved in the study were enrolled and divided into three groups, including control group, experimental group, and complication group. Numbers of CD3(+), CD4(+) and CD8(+) T cells and CD4(+)CD25(+)CDl27(low/-) Treg cells in the peripheral blood of patients before surgery, 1 month, 6 months, 1 year, and 2 years after surgery were analyzed by fluorescence active cell sorting (FACS). Contents of immunoglobulins (IgA, IgG and IgM) were analyzed by auto immunoassay analyzer. RESULTS: In the peripheral blood of patients from experimental group, numbers of CD3(+), CD4(+) and CD8(+) T cells initially declined, but afterwards increased to normal level; in the peripheral blood of patients from complication group, CD3(+) and CD8(+) T cells showed the same trend, but the number of CD4(+) T cells was below normal level at all detection times. Furthermore, CD3(+), CD4(+) and CD8(+) T cells in the peripheral blood of patients from complication group were initially less than those in experimental group, and afterwards were comparable between two groups. In patients from both experimental group and complication group, the number of CD4(+) CD25(+) CDl27(low/-)Treg cells increased 1 month and 6 months after surgery, and gradually restored to normal level. CD4(+)CD25(+)CDl27(low/-) Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery, but then they were comparable. Furthermore, contents of immunoglobulins (IgA, IgG and IgM) were comparable in three groups at all detection times. CONCLUSION: Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal. Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications.

The Impact of Climate on the Spread of Rice to North-Eastern China: A New Look at the Data from Shandong Province.

Moving crops outside of their original centers of domestication was sometimes a challenging process. Because of its substantial heat requirements, moving rice agriculture outside of its homelands of domestication was not an easy process for farmers in the past. Using crop niche models, we examine the constraints faced by ancient farmers and foragers as they moved rice to its most northerly extent in Ancient China: Shandong province. Contrary to previous arguments, we find that during the climatic optimum rice could have been grown in the region. Climatic cooling following this date had a clear impact on the distribution of rice, one that may have placed adaptive pressure on rice to develop a temperate phenotype. Following the development of this temperate phenotype, rice agriculture could once again become implanted in select areas of north-eastern China.